Preclinical pharmacodynamic and pharmacokinetic studies of investigational new drugs. Annual report, 1 November 1993-31 October 1994
During the past year of this contract pharmacokinetic, pharmacodynamic, bioavailability and metabolism studies have been conducted on two anti-cyanotic agents (WR242511 and p-aminohetanophenone (PAHP)) and one nerve agent antidote (HI-6) which are under consideration for clinical development by the U.S. Army. Radiolabeled formulations of WR242511, PAHP and HI-6 were used in these investigations. Information has been obtained on the half-lives of absorption and elimination of both radioactivity and the parent compound following oral and i.v. administration of these three compounds to dogs and, for PAHP, also to rats. In addition, the rates and extent of urinary and fecal elimination of the agents has been characterized; the pharmacodynamics, as assessed by the production of methemoglobin, of two compounds (WR242511 and PAHP) has been studied; and the metabolism of each compound has been investigated. Data obtained to date indicate that: WR242511 does not directly produce methemoglobinemia but a metabolite sequestered in red cells is the responsible agent; dogs appear to metabolize PAHP differently than do rats; the major urinary metabolite of HI-6 is 2-pyridine aldoxime. Further efforts to isolate and identify the metabolites of all three compounds are in progress.
- Research Organization:
- Southern Research Inst., Birmingham, AL (United States)
- OSTI ID:
- 80551
- Report Number(s):
- AD-A-288878/2/XAB; SRI-CBE-94-873; CNN: Contract DAMD17-93-C-3004; TRN: 51991452
- Resource Relation:
- Other Information: PBD: 11 Nov 1994
- Country of Publication:
- United States
- Language:
- English
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